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新冠病毒-宿主网络的外围和核心区域。

The peripheral and core regions of virus-host network of COVID-19.

机构信息

School of Computer Science and Technology, Xidian University, Xi'an 710071, China.

出版信息

Brief Bioinform. 2021 Nov 5;22(6). doi: 10.1093/bib/bbab169.

Abstract

Two thousand nineteen novel coronavirus SARS-CoV-2, the pathogen of COVID-19, has caused a catastrophic pandemic, which has a profound and widespread impact on human lives and social economy globally. However, the molecular perturbations induced by the SARS-CoV-2 infection remain unknown. In this paper, from the perspective of omnigenic, we analyze the properties of the neighborhood perturbed by SARS-CoV-2 in the human interactome and disclose the peripheral and core regions of virus-host network (VHN). We find that the virus-host proteins (VHPs) form a significantly connected VHN, among which highly perturbed proteins aggregate into an observable core region. The non-core region of VHN forms a large scale but relatively low perturbed periphery. We further validate that the periphery is non-negligible and conducive to identifying comorbidities and detecting drug repurposing candidates for COVID-19. We particularly put forward a flower model for COVID-19, SARS and H1N1 based on their peripheral regions, and the flower model shows more correlations between COVID-19 and other two similar diseases in common functional pathways and candidate drugs. Overall, our periphery-core pattern can not only offer insights into interconnectivity of SARS-CoV-2 VHPs but also facilitate the research on therapeutic drugs.

摘要

2019 年新型冠状病毒 SARS-CoV-2 是 COVID-19 的病原体,它在全球范围内对人类生活和社会经济造成了灾难性的影响。然而,SARS-CoV-2 感染引起的分子扰动仍然未知。在本文中,我们从全基因组的角度分析了 SARS-CoV-2 在人类相互作用组中扰动的邻域特性,并揭示了病毒-宿主网络 (VHN) 的外围和核心区域。我们发现,病毒-宿主蛋白 (VHP) 形成了一个显著连接的 VHN,其中高度扰动的蛋白聚集形成了一个可观察到的核心区域。VHN 的非核心区域形成了一个大规模但相对低扰动的外围区域。我们进一步验证了外围区域是不可忽视的,有利于识别 COVID-19 的合并症和检测药物再利用的候选药物。我们特别提出了一个基于 COVID-19、SARS 和 H1N1 的外围区域的花型模型,该模型显示了 COVID-19 与其他两种类似疾病在共同功能途径和候选药物方面的更多相关性。总的来说,我们的外围-核心模式不仅可以深入了解 SARS-CoV-2 VHP 的相互连接性,还可以促进治疗药物的研究。

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